Cocaine dependent (CD) subjects demonstrate great variability in response to cocaine cues presented in laboratory settings. Recognizing the clinical relevance, researchers have further examined this variability. Approximately half of CD subjects display changes in self report craving and the other half show little or no response. We have previously termed these groups high and low cue-reactive, respectively. This proposed exploratory I/START will move beyond documenting differences in high and low cue-reactivity via self report craving to objectively examining the consequences on cognitive control in response to drug and neutral cues using a modified antisaccade task, and fMRI to explore corresponding neural networks involved in cognitive control over cue-elicited behavior. This project is consistent with the I/START goals of pilot data collection, while also enabling Dr. Smelson to develop expertise in neuroimaging to enhance his research in drug craving, and expanding Dr. DiGirolamo's expertise in behavioral control and neuroimaging into the field of addiction. This project investigates the following Aims: 1. To examine differences in cognitive control toward cocaine cues based on differences in higher and lower cue reactivity; and 2. To evaluate neuroanatomical activation differences in cognitive control toward cocaine cues in high and low cue-reactive cocaine-dependent patients. Sixty-eight CD subjects will have a baseline cue-exposure procedure, followed by a modified antisaccade task to answer Aim 1. A subgroup of 24 subjects (12 high and 12 low cue- reactive individuals) will then undergo a second modified antisaccade task during fMRI to test Aim 2. This project will innovatively link a subjective measure of cue-reactivity (i.e., self-report craving) with objective measures of cognitive control via a modified antisaccade task and neural activation via fMRI. This work will clarify whether higher cue-reactive subjects display worse cognitive control to cocaine cues while examining the corresponding neural differences when attempting to control cue-elicited behavior. Future research directions of this proposed work will focus on whether higher reactive patients are more vulnerable to relapse, and have a differential response to pharmacological and psychosocial interventions targeting cue-elicited reactivity and control over cue-elicited behavior. This research will also assist in further establishing these paradigms for routine use in clinical assessment and treatment planning. PUBLIC HEALTH RELEVANCE: Cocaine craving is considered an important component of ongoing use, but its role in predicting relapse remains unclear. This research study has broad implications for further substantiating cue-exposure and the antisaccade task as clinical tools to identify patients with high craving, poor control over behavior, and thus, greater risk for relapse